Numerous reports relate an excess of site specific cancers to chronic alcohol (i.e. ethanol) consumption. Two tissues that develop excess cancers in humans are the liver and the esophagus. However, the mechanism(s) by which alcohol produces excess cancers in these tissues is unknown. In fact, animal models to relate alcohol effects on mechanistic events to enhanced alcohol associated carcinogenesis are sorely lacking. This study proposes to develop appropriate animal models so that the role of ethanol in carcinogenesis is determined. It is unlikely that alcohol is carcinogenic per se. There is an abundance of data that suggests it is not. Therefore, it is generally assumed that alcohol modules the carcinogenic response to other chemicals. If this is the case, then alcohol may modify the initiation stages of chemical carcinogenesis or act as a promoter. This study proposes to determine if alcohol enhances the initiation of hepatocytes by diethylnitrosamine and of the esophageal cells by methylbenzylnitrosamine. Alternatively, it will also investigate if alcohol acts a promoter when administered after these two initiating agents. Ethanol is administered to rats as part of an isocaloric diet before and during, or after initiation. Studies focus on the development of animal models which will permit assessment of the carcinogenic process (i.e. formation of carcinogen altered foci and nodules as well as tumors) in both tissues. The study will establish a relationship on the incidence of preneoplastic lesions and tumors and consumption of ethanol. The results obtained so far are encouraging and seem to indicate that we have a good system for the study of alcohol-related carcinogenesis. The animal models and accompanying studies will help resolve many of the conflicting reports concerning the effect of chronic alcohol consumption on the carcinogenic process. They should also provide a data base which will contribute to the development of medical strategies to reduce the risk of alcohol-carcinogen interactions at the clinical level.